He was born in Faribault, Minnesota, the eldest of five children of Frank W. Sanford and his wife Alberta Nichols.
The Carnegie Institute of Washington approved plans by Lewis Boss for an observation station in South America, and Roscoe Sanford was selected to travel there as an assistant.
After returning to the United States, he went back to South America in 1911 as an assistant at the Lick southern station in Santiago, Chile.
He then spent two years on classified research before returning to Mount Wilson where he continued to contribute until 1956.
He published an atlas of the spectra for late-type Carbon stars, and also determined the spectral features of the isotope carbon-13.